Spandidos Publications Logo
  • About
    • About Spandidos
    • Aims and Scopes
    • Abstracting and Indexing
    • Editorial Policies
    • Reprints and Permissions
    • Job Opportunities
    • Terms and Conditions
    • Contact
  • Journals
    • All Journals
    • Oncology Letters
      • Oncology Letters
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • International Journal of Oncology
      • International Journal of Oncology
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Molecular and Clinical Oncology
      • Molecular and Clinical Oncology
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Experimental and Therapeutic Medicine
      • Experimental and Therapeutic Medicine
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • International Journal of Molecular Medicine
      • International Journal of Molecular Medicine
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Biomedical Reports
      • Biomedical Reports
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Oncology Reports
      • Oncology Reports
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Molecular Medicine Reports
      • Molecular Medicine Reports
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • World Academy of Sciences Journal
      • World Academy of Sciences Journal
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • International Journal of Functional Nutrition
      • International Journal of Functional Nutrition
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • International Journal of Epigenetics
      • International Journal of Epigenetics
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Medicine International
      • Medicine International
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
  • Articles
  • Information
    • Information for Authors
    • Information for Reviewers
    • Information for Librarians
    • Information for Advertisers
    • Conferences
  • Language Editing
Spandidos Publications Logo
  • About
    • About Spandidos
    • Aims and Scopes
    • Abstracting and Indexing
    • Editorial Policies
    • Reprints and Permissions
    • Job Opportunities
    • Terms and Conditions
    • Contact
  • Journals
    • All Journals
    • Biomedical Reports
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Experimental and Therapeutic Medicine
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • International Journal of Epigenetics
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • International Journal of Functional Nutrition
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • International Journal of Molecular Medicine
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • International Journal of Oncology
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Medicine International
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Molecular and Clinical Oncology
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Molecular Medicine Reports
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Oncology Letters
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Oncology Reports
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • World Academy of Sciences Journal
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
  • Articles
  • Information
    • For Authors
    • For Reviewers
    • For Librarians
    • For Advertisers
    • Conferences
  • Language Editing
Login Register Submit
  • This site uses cookies
  • You can change your cookie settings at any time by following the instructions in our Cookie Policy. To find out more, you may read our Privacy Policy.

    I agree
Search articles by DOI, keyword, author or affiliation
Search
Advanced Search
presentation
Molecular Medicine Reports
Join Editorial Board Propose a Special Issue
Print ISSN: 1791-2997 Online ISSN: 1791-3004
Journal Cover
March-2018 Volume 17 Issue 3

Full Size Image

Sign up for eToc alerts
Recommend to Library

Journals

International Journal of Molecular Medicine

International Journal of Molecular Medicine

International Journal of Molecular Medicine is an international journal devoted to molecular mechanisms of human disease.

International Journal of Oncology

International Journal of Oncology

International Journal of Oncology is an international journal devoted to oncology research and cancer treatment.

Molecular Medicine Reports

Molecular Medicine Reports

Covers molecular medicine topics such as pharmacology, pathology, genetics, neuroscience, infectious diseases, molecular cardiology, and molecular surgery.

Oncology Reports

Oncology Reports

Oncology Reports is an international journal devoted to fundamental and applied research in Oncology.

Experimental and Therapeutic Medicine

Experimental and Therapeutic Medicine

Experimental and Therapeutic Medicine is an international journal devoted to laboratory and clinical medicine.

Oncology Letters

Oncology Letters

Oncology Letters is an international journal devoted to Experimental and Clinical Oncology.

Biomedical Reports

Biomedical Reports

Explores a wide range of biological and medical fields, including pharmacology, genetics, microbiology, neuroscience, and molecular cardiology.

Molecular and Clinical Oncology

Molecular and Clinical Oncology

International journal addressing all aspects of oncology research, from tumorigenesis and oncogenes to chemotherapy and metastasis.

World Academy of Sciences Journal

World Academy of Sciences Journal

Multidisciplinary open-access journal spanning biochemistry, genetics, neuroscience, environmental health, and synthetic biology.

International Journal of Functional Nutrition

International Journal of Functional Nutrition

Open-access journal combining biochemistry, pharmacology, immunology, and genetics to advance health through functional nutrition.

International Journal of Epigenetics

International Journal of Epigenetics

Publishes open-access research on using epigenetics to advance understanding and treatment of human disease.

Medicine International

Medicine International

An International Open Access Journal Devoted to General Medicine.

Journal Cover
March-2018 Volume 17 Issue 3

Full Size Image

Sign up for eToc alerts
Recommend to Library

  • Article
  • Citations
    • Cite This Article
    • Download Citation
    • Create Citation Alert
    • Remove Citation Alert
    • Cited By
  • Similar Articles
    • Related Articles (in Spandidos Publications)
    • Similar Articles (Google Scholar)
    • Similar Articles (PubMed)
  • Download PDF
  • Download XML
  • View XML
Article Open Access

Identifying hub genes and potential mechanisms associated with senescence in human annulus cells by gene expression profiling and bioinformatics analysis

  • Authors:
    • Chao Liu
    • Nong Chen
    • Kai Huang
    • Minbo Jiang
    • He Liang
    • Zhongyi Sun
    • Jiwei Tian
    • Deguo Wang
  • View Affiliations / Copyright

    Affiliations: Department of Orthopaedics, The Central Hospital of Songjiang, Shanghai 201600, P.R. China, Department of Orthopaedics, Qingpu Branch of Zhongshan Hospital Affiliated to Fudan University, Shanghai 201700, P.R. China, Department of Orthopaedics, Shanghai General Hospital of Nanjing Medical University, Shanghai 201620, P.R. China, Department of Orthopaedics, Shanghai Fengxian Hospital, Shanghai 201400, P.R. China, Department of Orthopaedics, Shanghai Jiao Tong University Affiliated First People's Hospital, Shanghai 201620, P.R. China
    Copyright: © Liu et al. This is an open access article distributed under the terms of Creative Commons Attribution License.
  • Pages: 3465-3472
    |
    Published online on: December 20, 2017
       https://doi.org/10.3892/mmr.2017.8322
  • Expand metrics +
Metrics: Total Views: 0 (Spandidos Publications: | PMC Statistics: )
Metrics: Total PDF Downloads: 0 (Spandidos Publications: | PMC Statistics: )
Cited By (CrossRef): 0 citations Loading Articles...

This article is mentioned in:



Abstract

The aim of the present study was to reveal the potential hub genes and regulatory mechanisms associated with senescence in human annulus cells by analyzing microarray data using bioinformatics. The gene expression dataset GSE17077, of senescent and non‑senescent annulus cells obtained from patients with disc degenerative diseases (DDD), was downloaded from the Gene Expression Omnibus database. Differentially expressed genes (DEGs) were identified. Functional and pathway annotations were performed using Gene Ontology and Kyoto Encyclopedia of Genes and Genomes terms, respectively. Web‑based Gene Set Analysis Toolkit and Chip Enrichment Analysis were used to identify key transcription factors (TFs). A protein‑protein interaction (PPI) network was constructed to analyze the hub genes associated with senescence in DDD. A total of 667 DEGs were screened, including 368 up‑ and 299 down‑regulated genes. These DEGs were enriched in phosphorylation, regulation of apoptosis and regulation of programmed cell death. In addition, DEGs were involved in axon guidance, natural killer cell‑mediated cytotoxicity, purine metabolism and the mitogen‑activated protein kinase (MAPK) signaling pathway. The TFs activator protein 1 (AP1), specificity protein 1 and aryl hydrocarbon receptor may serve regulatory roles in gene expression in senescent cells. Certain key target genes of TFs, including heat shock protein 90 (HSP90) and C‑X‑C motif chemokine 5 (CXCL5), within the DEGs were revealed to have a high connectivity degree by PPI analysis. The results of the present study indicated that the MAPK‑regulated AP1 pathway may contribute to senescence‑associated disc degeneration. The DEGs, including HSP90 and CXCL5, with a high degree of connectivity may be potential targets for future investigations into molecular biomarkers.
View Figures

Figure 1

Figure 2

Figure 3

Figure 4

Figure 5

Figure 6

View References

1 

Katz JN: Lumbar disc disorders and low-back pain: Socioeconomic factors and consequences. J Bone Joint Surg Am. 88 Suppl 2:S21–S24. 2006. View Article : Google Scholar

2 

Hoy D, Bain C, Williams G, March L, Brooks P, Blyth F, Woolf A, Vos T and Buchbinder R: A systematic review of the global prevalence of low back pain. Arthritis Rheum. 64:2028–2037. 2012. View Article : Google Scholar : PubMed/NCBI

3 

Luoma K, Riihimäki H, Luukkonen R, Raininko R, Viikari-Juntura E and Lamminen A: Low back pain in relation to lumbar disc degeneration. Spine (Phila Pa 1976). 25:487–492. 2000. View Article : Google Scholar : PubMed/NCBI

4 

Saltychev M, Eskola M and Laimi K: Lumbar fusion compared with conservative treatment in patients with chronic low back pain: A meta-analysis. Int J Rehabil Res. 37:2–8. 2014. View Article : Google Scholar : PubMed/NCBI

5 

Walter BA, Korecki CL, Purmessur D, Roughley PJ, Michalek AJ and Iatridis JC: Complex loading affects intervertebral disc mechanics and biology. Osteoarthritis Cartilage. 19:1011–1018. 2011. View Article : Google Scholar : PubMed/NCBI

6 

Risbud MV and Shapiro IM: Role of cytokines in intervertebral disc degeneration: Pain and disc content. Nat Rev Rheumatol. 10:44–56. 2014. View Article : Google Scholar : PubMed/NCBI

7 

Gruber HE, Ingram JA, Norton HJ and Hanley EN Jr: Senescence in cells of the aging and degenerating intervertebral disc: Immunolocalization of senescence-associated beta-galactosidase in human and sand rat discs. Spine (Phila Pa 1976). 32:321–327. 2007. View Article : Google Scholar : PubMed/NCBI

8 

Kim KW, Chung HN, Ha KY, Lee JS and Kim YY: Senescence mechanisms of nucleus pulposus chondrocytes in human intervertebral discs. Spine J. 9:658–666. 2009. View Article : Google Scholar : PubMed/NCBI

9 

Gruber HE, Hoelscher GL, Ingram JA, Zinchenko N and Hanley EN Jr: Senescent vs. non-senescent cells in the human annulus in vivo: Cell harvest with laser capture microdissection and gene expression studies with microarray analysis. BMC Biotechnol. 10:52010. View Article : Google Scholar : PubMed/NCBI

10 

Irizarry RA, Hobbs B, Collin F, Beazer-Barclay YD, Antonellis KJ, Scherf U and Speed TP: Exploration, normalization, and summaries of high density oligonucleotide array probe level data. Biostatistics. 4:249–264. 2003. View Article : Google Scholar : PubMed/NCBI

11 

Fujita A, Sato JR, Rodrigues Lde O, Ferreira CE and Sogayar MC: Evaluating different methods of microarray data normalization. BMC Bioinformatics. 7:4692006. View Article : Google Scholar : PubMed/NCBI

12 

Ritchie ME, Silver J, Oshlack A, Holmes M, Diyagama D, Holloway A and Smyth GK: A comparison of background correction methods for two-colour microarrays. Bioinformatics. 23:2700–2707. 2007. View Article : Google Scholar : PubMed/NCBI

13 

Eisen MB, Spellman PT, Brown PO and Botstein D: Cluster analysis and display of genome-wide expression patterns. Proc Natl Acad Sci USA. 95:pp. 14863–14868. 1998; View Article : Google Scholar : PubMed/NCBI

14 

Ashburner M, Ball CA, Blake JA, Botstein D, Butler H, Cherry JM, Davis AP, Dolinski K, Dwight SS, Eppig JT, et al: Gene ontology: Tool for the unification of biology. The Gene Ontology Consortium. Nat Genet. 25:25–29. 2000. View Article : Google Scholar : PubMed/NCBI

15 

Huang da W, Sherman BT and Lempicki RA: Bioinformatics enrichment tools: Paths toward the comprehensive functional analysis of large gene lists. Nucleic Acids Res. 37:1–13. 2009. View Article : Google Scholar : PubMed/NCBI

16 

von Mering C, Huynen M, Jaeggi D, Schmidt S, Bork P and Snel B: STRING: A database of predicted functional associations between proteins. Nucleic Acids Res. 31:258–261. 2003. View Article : Google Scholar : PubMed/NCBI

17 

Shannon P, Markiel A, Ozier O, Baliga NS, Wang JT, Ramage D, Amin N, Schwikowski B and Ideker T: Cytoscape: A software environment for integrated models of biomolecular interaction networks. Genome Res. 13:2498–2504. 2003. View Article : Google Scholar : PubMed/NCBI

18 

Nasto LA, Robinson AR, Ngo K, Clauson CL, Dong Q, St Croix C, Sowa G, Pola E, Robbins PD, Kang J, et al: Mitochondrial-derived reactive oxygen species (ROS) play a causal role in aging-related intervertebral disc degeneration. J Orthop Res. 31:1150–1157. 2013. View Article : Google Scholar : PubMed/NCBI

19 

Le Maitre CL, Freemont AJ and Hoyland JA: Accelerated cellular senescence in degenerate intervertebral discs: A possible role in the pathogenesis of intervertebral disc degeneration. Arthritis Res Ther. 9:R452007. View Article : Google Scholar : PubMed/NCBI

20 

Hiyama A, Gogate SS, Gajghate S, Mochida J, Shapiro IM and Risbud MV: BMP-2 and TGF-beta stimulate expression of beta1,3-glucuronosyl transferase 1 (GlcAT-1) in nucleus pulposus cells through AP1, TonEBP and Sp1: role of MAPKs. J Bone Miner Res. 25:1179–1190. 2010.PubMed/NCBI

21 

Sepulveda JC, Tomé M, Fernández ME, Delgado M, Campisi J, Bernad A and González MA: Cell senescence abrogates the therapeutic potential of human mesenchymal stem cells in the lethal endotoxemia model. Stem cells. 32:1865–1877. 2014. View Article : Google Scholar : PubMed/NCBI

22 

Kim YJ, Hwang SH, Lee SY, Shin KK, Cho HH, Bae YC and Jung JS: miR-486-5p induces replicative senescence of human adipose tissue-derived mesenchymal stem cells and its expression is controlled by high glucose. Stem Cells Dev. 21:1749–1760. 2012. View Article : Google Scholar : PubMed/NCBI

23 

Chan KC, Ting CM, Chan PS, Lo MC, Lo KW, Curry JE, Smyth T, Lee AW, Ng WT, Tsao GS, et al: A novel Hsp90 inhibitor AT13387 induces senescence in EBV-positive nasopharyngeal carcinoma cells and suppresses tumor formation. Mol Cancer. 12:1282013. View Article : Google Scholar : PubMed/NCBI

24 

Wang J, Tian Y, Phillips KL, Chiverton N, Haddock G, Bunning RA, Cross AK, Shapiro IM, Le Maitre CL and Risbud MV: Tumor necrosis factor α- and interleukin-1β-dependent induction of CCL3 expression by nucleus pulposus cells promotes macrophage migration through CCR1. Arthritis Rheum. 65:832–842. 2013. View Article : Google Scholar : PubMed/NCBI

25 

Kawaguchi S, Yamashita T, Katahira G, Yokozawa H, Torigoe T and Sato N: Chemokine profile of herniated intervertebral discs infiltrated with monocytes and macrophages. Spine (Phila Pa 1976). 27:1511–1516. 2002. View Article : Google Scholar : PubMed/NCBI

26 

Acosta JC, O'Loghlen A, Banito A, Guijarro MV, Augert A, Raguz S, Fumagalli M, Da Costa M, Brown C, Popov N, et al: Chemokine signaling via the CXCR2 receptor reinforces senescence. Cell. 133:1006–1018. 2008. View Article : Google Scholar : PubMed/NCBI

27 

Roughley PJ: Biology of intervertebral disc aging and degeneration: Involvement of the extracellular matrix. Spine (Phila Pa 1976). 29:2691–2699. 2004. View Article : Google Scholar : PubMed/NCBI

Related Articles

  • Abstract
  • View
  • Download
  • Twitter
Copy and paste a formatted citation
Spandidos Publications style
Liu C, Chen N, Huang K, Jiang M, Liang H, Sun Z, Tian J and Wang D: Identifying hub genes and potential mechanisms associated with senescence in human annulus cells by gene expression profiling and bioinformatics analysis. Mol Med Rep 17: 3465-3472, 2018.
APA
Liu, C., Chen, N., Huang, K., Jiang, M., Liang, H., Sun, Z. ... Wang, D. (2018). Identifying hub genes and potential mechanisms associated with senescence in human annulus cells by gene expression profiling and bioinformatics analysis. Molecular Medicine Reports, 17, 3465-3472. https://doi.org/10.3892/mmr.2017.8322
MLA
Liu, C., Chen, N., Huang, K., Jiang, M., Liang, H., Sun, Z., Tian, J., Wang, D."Identifying hub genes and potential mechanisms associated with senescence in human annulus cells by gene expression profiling and bioinformatics analysis". Molecular Medicine Reports 17.3 (2018): 3465-3472.
Chicago
Liu, C., Chen, N., Huang, K., Jiang, M., Liang, H., Sun, Z., Tian, J., Wang, D."Identifying hub genes and potential mechanisms associated with senescence in human annulus cells by gene expression profiling and bioinformatics analysis". Molecular Medicine Reports 17, no. 3 (2018): 3465-3472. https://doi.org/10.3892/mmr.2017.8322
Copy and paste a formatted citation
x
Spandidos Publications style
Liu C, Chen N, Huang K, Jiang M, Liang H, Sun Z, Tian J and Wang D: Identifying hub genes and potential mechanisms associated with senescence in human annulus cells by gene expression profiling and bioinformatics analysis. Mol Med Rep 17: 3465-3472, 2018.
APA
Liu, C., Chen, N., Huang, K., Jiang, M., Liang, H., Sun, Z. ... Wang, D. (2018). Identifying hub genes and potential mechanisms associated with senescence in human annulus cells by gene expression profiling and bioinformatics analysis. Molecular Medicine Reports, 17, 3465-3472. https://doi.org/10.3892/mmr.2017.8322
MLA
Liu, C., Chen, N., Huang, K., Jiang, M., Liang, H., Sun, Z., Tian, J., Wang, D."Identifying hub genes and potential mechanisms associated with senescence in human annulus cells by gene expression profiling and bioinformatics analysis". Molecular Medicine Reports 17.3 (2018): 3465-3472.
Chicago
Liu, C., Chen, N., Huang, K., Jiang, M., Liang, H., Sun, Z., Tian, J., Wang, D."Identifying hub genes and potential mechanisms associated with senescence in human annulus cells by gene expression profiling and bioinformatics analysis". Molecular Medicine Reports 17, no. 3 (2018): 3465-3472. https://doi.org/10.3892/mmr.2017.8322
Follow us
  • Twitter
  • LinkedIn
  • Facebook
About
  • Spandidos Publications
  • Careers
  • Cookie Policy
  • Privacy Policy
How can we help?
  • Help
  • Live Chat
  • Contact
  • Email to our Support Team